1,4,7,10-Tetraazatetracyclo[5.5.1.04,13.010,13 ]tridecane and its conjugate acids

ABSTRACT

1,4,7,10-Tetraazatetracyclo[5.5.1.0 4 ,13.0 10 ,13 ]tridecane -tridecane which can reversibly and successively add two moles of acids to form conjugate acids, can be made by condensation of 1,4,7,10-tetraazacyclododecane with ethyl orthocarbonate or by the condensation of 2,3,5,6-tetrahydro-1H-imidazo[1,2-a]imidazole with ethyl bis(2-chloroethyl)carbamate followed by acid hydrolysis. The salts with acids having photographically innocuous anions can be used in developers for silver halide emulsion to reduce fog, and can be used in the emulsions themselves as sensitizers.

FIELD OF THE INVENTION

This invention relates to a novel tetracyclic tetraamine and itstricyclic salts made by reaction of the tetraamine with acids havingphotographically innocuous anions.

DESCRIPTION OF THE INVENTION

This invention is directed to the tetraamine1,4,7,10-tetraazatetracyclo[5.5.1.0⁴,13.0¹⁰,13 ]tridecane (formula I),to its salts with one or two equivalents of an acid having aphotographically innocuous anion, to developer for silver halideemulsions containing an amount of the tetraamine or its salts sufficientto reduce background fog, and to the use of such compounds inphotographic silver halide emulsions in an amount sufficient tosensitize said emulsion.

The tetraamine of this invention and its equilibrium with the salts1,2,3,4,6,7,8,9-octahydro-5H-4a-azonia-2a,7,9a-triazacycloocta[cd]pentalenechloride (formula II) and1,2,3,4,6,7,8,9-octahydro-5H-4a-azonia-2a,7,9a-triazacycloocta[cd]pentalenechloride hydrochloride (formula III) in the presence of hydrochloricacid, which are preferred salts is shown in the following equation:##SPC1##

The interconversions depicted in the preceding equation all take placerapidly at room temperature. Treatment of I with one equivalent ofhydrochloric acid produces II; treatment of II with one equivalent of astrong base such as aqueous sodium hydroxide reconverts II to I.Treatment of II with one or more equivalents of hydrochloric acidproduces III; treatment of III with one equivalent of a strong base suchas aqueous sodium hydroxide converts it to II. I and III can beinterconverted directly without stopping at II; i.e., by treating I withtwo or more equivalents of hydrochloric acid and by treating III withtwo or more equivalents of sodium hydroxide.

The organic, cationic moieties of II and III are the monoprotonated anddiprotonated conjugate acids of I, respectively. Correspondingly, I isthe conjugate base formed by removing one proton from the cation of IIor two protons from the cation of III. The facile equilibrium betweenthe base I and the conjugate acids II and III is unusual, in that a C-Nbond is broken and reformed in the processes. Usually there is no suchbond rupture in the interconversions of conjugate acids and bases.

In II the unit positive charge assigned to one of the ring nitrogenatoms is actually shared by the three nitrogens bonded to the centralcarbon, and to a lesser extent by the central carbon, to give aresonance-stabilized structure. The structure shown for II is one ofseveral localized structures contributing to the overall structure. Itis used both for convenience and to make it easier to name the compound.The same is true for the corresponding unit positive charge in III.

The tetraamine of the invention and its chloride salts can be preparedas shown in the following examples. Of the starting materials used inExample A, 2,3,5,6-tetrahydro-1H-imidazo[1,2-a]imidazole was preparedessentially by the method of McKay et al., J. Am. Chem. Soc. 78, 6144(1956), and was purified by recrystallization from acetonitrile; ethylbis(2-chloroethyl)carbamate was prepared by the method of Skipper etal., J. Nat. Cancer Inst. 9, 77 (1948).

Salts of other acids such as sulfuric acid, nitric acid, acetic acid,tartaric acid and lactic acid having photographically innocuous anionscan be made by conventional metathetic reactions.

The term "photographically innocuous anion" is intended to mean an anionwhose presence in a photographic silver halide emulsion and/or in adeveloper solution therefor, has little or no effect on the photographicprocess.

This invention is further illustrated by the following examples whichare not intended to be limiting.

EXAMPLE A7-Ethoxycarbonyl-1,2,3,4,6,7,8,9-octahydro-5H-4a-azonia-2a,7,9a-triazacycloocta[cd]pentalenetetraphenylborate ##SPC2##

To a stirred solution of 3.11 g of ethyl bis(2-chloroethyl)carbamate in30 ml of dry dimethylformamide was added 1.62 g of2,3,5,6-tetrahydro-1H-imidazo[1,2-a]imidazole. The mixture was warmeduntil it became homogeneous (ca. 40°-50°C). On cooling, the startingimidazole crystallized, and the reaction mixture remained stronglybasic. The mixture was still strongly basic after stirring at 70°-80°Cfor 5 minutes and after stirring at 100°C for 15 minutes. It was heatedat about 100°C on a steam bath for 2.5 hours, after which titration of a1.0-ml sample with 0.1 N HCl showed that 65% of the original base hadbeen neutralized. Heating on the steam bath was continued for 1.75hours, followed by stirring at ambient temperature overnight, afterwhich the mixture was only weakly basic to phenolphthalein. The absenceof basicity indicated that the first stage of the desired reaction,i.e., reaction of one of the 2-chloroethyl groups at the NH group of theimidazole with elimination of HCl, was essentially complete. The resultsalso indicated that heating the reaction mixture for one 6-hour periodat 100°C would suffice for this part of the process.

There was then added to the mixture 16.8 ml of 0.86 M potassiumt-butoxide in dimethylformamide, and the resulting slurry was heated at100°C with stirring for about 20 hours. The solution was concentratedunder reduced pressure to give 4.4 g of an oil, of which 3.5 g wasdissolved in water and treated with excess aqueous sodiumtetraphenylborate. The white solid that precipitated was separated byfiltration, washed with ethyl alcohol, and recrystallized fromacetonitrile, to give 2.17 g of7-ethoxycarbonyl-1,2,3,4,6,7,8,9-octahydro-5H-4a-azonia-2a,7,9a-triazacycloocta[cd]pentalenetetraphenylborate. A smaller sample of the product, similarly preparedfrom the nonvolatile oil and recrystallized from acetonitrile, melted at201.5°-203°C.

    ______________________________________                                        Anal. Calcd. for C.sub.36 H.sub.41 BN.sub.4 O.sub.2 :                                          C,    75.52;  H,  7.22;                                                                              N,  9.79                              Found:           C,    75.13;  H,  7.35;                                                                              N,  9.85                                                     74.86       7.24     9.89                              ______________________________________                                    

NMR (220 MHz, CD₃ CN): δ7.25 (m, 8H, meta), 6.99 (t, 8H, ortho), 6.82(t, 4H, para), 4.11 (quartet, 2H, CH₂,CH₃), 3.93, 3.66, 3.51 and 3.33(all triplets, 4H each) and 1.26 (t, 3H, CH₃).

A second recrystallization of this sample from acetonitrile gave mp201°-202°C and the following analytical data:

    Found:                                                                              C,    75.34;   H,  7.46;  N,  9.88                                                  75.04        7.42       9.61                                  

EXAMPLE 11,2,3,4,6,7,8,9-Octahydro-5H-4a-azonia-2,7,9a-triazacycloocta[cd]pentalenechloride hydrochloride ##SPC3##

a. The tetraphenylborate salt that was the product of Example A (2.0 g)was converted to the corresponding nitrate by dissolving it in 40 ml ofwarm acetonitrile and adding a solution of 0.60 g of silver nitrate in10 ml of acetonitrile. After 30 minutes the precipitated silvertetraphenylborate was separated by filtration, and the filtrate wasevaporated to give 1.12 g of crystalline nitrate. This was converted tothe corresponding chloride by dissolving it in water and passing thesolution through an anion-exchange column containing quaternary ammoniumchloride residues on crosslinked polystyrene ("Dowex" 2-X8). An aqueoussolution of the chloride in 20 ml of water was thus obtained. Theidentity of the product was confirmed by evaporating one-fifth of thissolution to give 199 mg of the chloride and observing the similarity ofthe aliphatic region of its nmr spectrum in D₂ O with the spectrum ofthe tetraphenylborate used as starting material.

Another one-fifth of the aqueous solution was saturated with hydrogenchloride at 25°C, and the resulting solution was heated in a sealedglass tube at 100°C for 60 hours. The resulting solution wasconcentrated under vacuum to give 110 mg of solid1,2,3,4,6,7,8,9-octahydro-5H-4a-azonia-2a,7,9a-triazacycloocta[cd]pentalenechloride hydrochloride.

b. A larger sample of the product, prepared by the same method andwashed with isopropyl alcohol, melted at 149°-154°C. Recrystallizationfrom absolute ethyl alcohol gave colorless crystals, mp 151°-153°C.These crystals were apparently a solvate, since on drying at about 80°Cin vacuum they became opaque and had mp 250°-252°C. The followinganalyses were carried out on the vacuum-dried sample.

Anal. Calcd. for C₉ H₁₈ Cl₂ N₄ : C, 42.69; H, 7.17; N, 22.13 Found: C,42.17; H, 6.83; N, 22.38.

IR(KBr, solvent-free): 2.92 (strong), 3.38, 3.45, 3.6-3.77 (severalbroad bands), 3.91, 4.20, 4.65 (weak), 5.95 (strong), 6.10 (weak), 6.24(strong), 6.72, 6.83, 7.21, 7.27, 7.54, 7.74 (strong), 8.31, 8.71, 9.02,9.18, 9.51, 10.05, 10.21, 10.45, 10.56, 11.7-12.2, 13.10, 14.25(shoulder) and 14.50μ (broad).

NMR (D₂ O): 27-line pattern composed of 2 overlapping symmetrical AA'BB'patterns with approximate shifts of (4.23 and 3.57 ppm) and (3.93 and3.67 ppm).

When excess aqueous sodium picrate solution was added to an aqueoussolution of a small amount of the product in a, a yellow dipicrateprecipitated, mp 245°-250°C (dec). In this compound the two chlorideions of the product of the example have been replaced by picrate ions.Another sample of the dipicrate, similarly prepared, was recrystallizedfrom acetonitrile; mp 255°-259°C (dec).

    __________________________________________________________________________    Anal. Calcd. for C.sub.21 H.sub.22 N.sub.10 O.sub.14 :                                         C,                                                                              39.50,                                                                             H,                                                                              3.47;                                                                              N,                                                                              21.94                                        Found:           C,                                                                              40.14;                                                                             H,                                                                              3.49;                                                                              N,                                                                              21.78                                                           39.96  3.49   21.72                                        __________________________________________________________________________

An infrared absorption spectrum of the picrate was also obtained.

EXAMPLE 2 1,4,7,10-Tetraazatetracyclo[5.5.1.0⁴,13.0¹⁰,13 ]tridecane##SPC4##

To a solution of 110 mg of1,2,3,4,6,7,8,9-octahydro-5H-4a-azonia-2a,7,9a-triazacycloocta[cd]pentalenechloride hydrochloride in 0.5 ml of D₂ O was added 0.3 g of a 14% (byweight) solution of sodium hydroxide in D₂ O and then 0.4 ml ofchloroform-d. The mixture was shaken thoroughly, and the organic phasewas allowed to settle out. The nmr absorption spectrum of the organicphase showed a single symmetrical A₂ B₂ pattern shifted to higher fieldsthan the complex pattern of the starting material. Evaporation of theorganic phase gave 1,4,7,10-tetraazacyclo[5.5.1.0⁴,13.0¹⁰,13 ]tridecaneas a white solid. When an aqueous solution of the product was acidifiedwith excess aqueous picric acid, a yellow solid precipitated. The latterproduct had an infrared absorption spectrum identical with that of thedipicrate described in Example 1. It melted at 240°-245°C (dec).

EXAMPLE 3 1,4,7,10-Tetraazatetracyclo[5.5.1.0⁴,13.0¹⁰,13 ]tridecane

a. A solution of 6.7 g of1,2,3,4,6,7,8,9-octahydro-5H-4a-azonia-2a,7,9a-triazacycloocta[cd]pentalenechloride hydrochloride in 50 ml of water was prepared by scaling up themethod of Example 1. Enough sodium hydroxide was dissolved in 40 ml ofthis solution to make it strongly basic. The resulting solution wasextracted with several portions of chloroform, and the combined extractswere dried over 3A molecular sieves for 50 minutes. The infraredabsorption spectrum of the chloroform solution indicated that water ofhydration was still present after this treatment. The chloroform wasremoved by distillation under nitrogen. The residue was heated in abulb-to-bulb distillation apparatus at 70°-110°C (oven temperature) and2 mm and then at 110°-150°C at 9 mm. A total of 2.55 g of1,4,7,10-tetraazatetracyclo[5.5.1.0⁴,13.0¹⁰,13 ]tridecane volatilized asa solid sublimate and a semisolid distillate. The distillate soon becameentirely solid. A sample of the sublimate melted at 97°-104.5°C and gavethe following analyses:

NMR (CCl₄): Symmetrical AA'BB' pattern, 14 lines centered at δ2.83.

NMR (CD₃ CN): Broad singlet (width at half height ˜8 Hz) at δ2.83 at35°C splitting to a broadened symmetrical multiplet at -30°C.

Mass Spectrum: m/e (rel. intensity) 180 (100, parent peak), 179 (10),152 (30-40), 138 (15-20), 124 (80-90), 110 (15-20), 98 (40-50), 56(20-30), 55 (15-20) and 42 (20-25).

Titration with hydrochloric acid gave two end points by glass-electrodepotentiometry, corresponding to an equivalent weight of 91 ± 9 and amolecular weight of 182 ± 18 for a dibasic amine. The calculated valuesfor C₉ H₁₆ N₄ are 90 and 180, respectively.

b. 1,4,7,10-Tetraazatetracyclo[5.5.1.0⁴,13.0¹⁰,13 ]tridecane wasprepared essentially by the method described above and was distilled ina bulb-to-bulb apparatus at about 140°C/7 mm. The colorless solid meltedat 105°-108°C. Analysis indicated that the product was a hydratecontaining an average of 0.73 molecule of water per molecule oftetraamine.

    __________________________________________________________________________    Anal. Calcd. for C.sub.9 H.sub.16 N.sub.4.0.73 H.sub.2 O:                                        C,                                                                              55.88;                                                                             H,                                                                              9.10;                                                                              N,                                                                              28.97                                      Found:             C,                                                                              56.00;                                                                             H,                                                                              8.86;                                                                              N,                                                                              29.03                                                           55.70  8.96   29.32                                      __________________________________________________________________________

Acidification of an aqueous solution of the product with excess aqueouspicric acid caused a yellow dipicrate to precipitate. The latter wasrecrystallized three times from aqueous acetonitrile, after which itmelted at 255°-259°C (dec) and was shown to be identical with thepicrates described in Examples 1 and 2 by comparison of the infraredabsorption spectra.

    __________________________________________________________________________    Anal. Calcd. for C.sub.21 H.sub.22 N.sub.10 O.sub.14 :                                         C,                                                                              39.50;                                                                             H,                                                                              3.47;                                                                              N,                                                                              21.94                                        Found:           C,                                                                              39.52;                                                                             H,                                                                              3.17;                                                                              N,                                                                              21.60                                                           39.97  3.28   21.85                                                           39.56  3.17   21.65                                        __________________________________________________________________________

IR (KBr): 2.9 (broad), 3.2-4.0 (broad), 5.90, 6.08, 6.17, 6.37, 6.96,7.32, 7.57 (broad), 7.87, 8.60, 9.26, 9.52, 11.0, 12.69, 13.44, and14.10μ.

EXAMPLE 4

1,2,3,4,6,7,8,9-Octahydro-5H-4a-azonia-2a,7,9a-triazacycloocta[cd]pentalenechloride ##SPC5##

A mixture of 0.52 g of 1,4,7,10-tetraazacyclododecane, 0.32 g oftetraazacyclododecane tetrahydrochloride, 0.77 g of ethylorthocarbonate, and 5 ml of absolute ethyl alcohol was heated withstirring on a steam bath (ca. 100°C) for 8 hours. The nmr spectrum of asmall sample of the mixture indicated that the desired reaction wasabout 75-80% complete. The mixture was heated with stirring on a steambath for 19 hours more. Volatile materials were evaporated under reducedpressure, and the residue was recrystallized from acetonitrile to give0.20 g of1,2,3,4,6,7,8,9-octahydro-5H-4a-azonia-2a,7,9a-triazacycloocta[cd]pentalenechloride (II) as needle-like crystals.

A sample of the product was dissolved in warm perdeuteroacetonitrile.The nmr spectrum of the resulting solution consisted of only twoabsorptions, a broad singlet (width at 1/2 height 5.5 Hz) 1.53 ppmdownfield and a sharp singlet 0.83 ppm downfield from the solventabsorption. The low field absorption was assigned to the methyleneprotons of II, which are rapidly exchanging amongst the four differentlocations in structure II. This is evidence for the rapidinterconversion of I, II and III.

On standing the perdeuteroacetonitrile solution deposited clear, longneedles of1,2,3,4,6,7,8,9-octahydro-5H-4a-azonia-2a,7,9a-triazacycloocta[cd]pentalenechloride. The product was a monohydrate, mp 133°-136°C, which kept itswater of hydration on drying at 80°C and 0.1 mm.

    __________________________________________________________________________    Anal. Calcd. for C.sub.9 H.sub.17 N.sub.4 Cl.H.sub.2 O:                                          C,                                                                              46.05;                                                                             H,                                                                              8.15;                                                                              N,                                                                              23.87                                      Found:             C,                                                                              46.04;                                                                             H,                                                                              7.67;                                                                              N,                                                                              24.08                                                           46.08  7.99   24.05                                      __________________________________________________________________________

As previously noted, 1,4,7,10-tetraazatetracyclo[5.5.1.0⁴,13.0¹⁰,13]tridecane (I) can be made from the product of the foregoing example(II) by treatment with one or more equivalents of sodium hydroxide.Similarly, and as also previously noted,1,2,3,4,6,7,8,9-octahydro-5H-4a-azonia-2,7,9a-triazacycloocta[cd]pentalenechloride hydrochloride (III) can be made by treatment of the product ofthe foregoing example with one or more equivalents of hydrochloric acid.

1,4,7,10-Tetraazacyclododecane, the starting material in the foregoingexample, can be prepared by the method of Stetter and Mayer, Chem. Ber.94, 1410 (1961).

As illustrated in the following examples, the products of the inventionare useful as sensitizers in photographic emulsion systems, and can beemployed in developer systems for silver halide emulsion to reduce fog,to reduce the toe of the optical density/exposure curve, and to assistcontrast without substantial loss of speed.

EXAMPLE B

To an acidified solution of gelatin containing 1.5 moles of potassiumchloride there was rapidly added 1.5 moles of silver nitrate in aqueoussolution. There was then added 0.6 moles of aqueous potassium bromidesolution and the mixture allowed to ripen for ten minutes, after whichthere was added 0.9 moles of aqueous potassium bromide solution and themixture allowed to ripen for 10 minutes, all at 160°F. The resultingemulsion was cooled, coagulated, washed, and redispersed in the mannerdisclosed in Moede, U.S. Pat. No. 2,772,162 issued Nov. 27, 1956. Twoemulsions were made in this manner; number one a control as described,and number two a test containing 0.3 g of1,2,3,4,6,7,8,9-octahydro-5H-4a-azonia-2a,7,9a-triazacycloocta[cd]pentalenechloride hydrochloride (III) dissolved in the acidified solution ofgelatin before the silver nitrate solution was added.

The acidified gel solution contains 0.0768 moles of HCl, which issufficient to produce a pH ≅ 2 with 50 g of gelatin plus 1.5 moles ofKCl dissolved in 2564 ml of solution. The 0.3 g of the test compound isequal to 0.0012 moles based on formula III. The HCl present would havebeen adequate to produce the chloride hydrochloride in solution, andstill leave sufficient HCl to produce an acid "make", if the conjugatebase, 1,4,7,10-tetraazatetracyclo[5.5.1.0⁴,13.0¹⁰,13 ]tridecane (I), orthe chloride of its monoprotonated conjugate acid, II, had been used asthe test compound. Emulsions number one and number two were treated intwo different ways:

(1) Negative Acting Primitive Emulsion

To the emulsion containing silver halide equivalent to 1.5 moles ofsilver nitrate there was added 124 g of gelatin and the temperatureraised to 130°F. The pH was adjusted to 8 with borax and the emulsiondigested for 40 minutes at 130°F. The pH was then adjusted to 5.5,coating aids including a gelatin hardener added, and the emulsion coatedon a 4 mil polyester film support, and dried in the conventional manner.

A strip of each coated emulsion was exposed through a √2 wedge by meansof a quartz-iodine lamp that provided an exposure of 514,000meter-candle-seconds. It was then developed for 1.5 minutes at 80°F in acommercial hydroquinone-formaldehyde litho developer, and fixed, washed,and dried in a conventional manner. Densities were then read in aconventional densitometer. The results are shown in the following table.

    ______________________________________                                        RESPONSE OF NEGATIVE ACTING PRIMITIVE EMULSION                                ______________________________________                                        Make                                                                          Variation      D-Min            D-Max                                         ______________________________________                                        No. 1                                                                         Control        .03              .08                                           No. 2          .05              .35                                           ______________________________________                                    

The greater response of emulsion number two shows that III acts as asensitizer.

(2) Direct Positive Emulsion

To the emulsion containing silver halide equivalent to 1.5 moles ofsilver nitrate there was added 124 g of gelatin and the temperatureraised to 130°F. A chemical fogging agent was added as described inBigelow, U.S. Pat. No. 3,637,392 issued Jan. 25, 1972, the pH adjustedto 8 with borax and the mixture digested for 40 minutes at 130°F. The pHwas then adjusted to 5.5, coating aids including a gelatin hardeneradded, and the emulsion coated on a 4 mil polyester film support, driedin a conventional manner and tested by the procedure described in part(1). The results are shown in the following table.

    ______________________________________                                        RESPONSE OF DIRECT POSITIVE EMULSION                                          ______________________________________                                        Make                              Speed                                       Variation D-Min       D-Max       (D=1.0)                                     ______________________________________                                        No. 1                                                                         Control   .03         2.15        100                                         No. 2     .06         3.89         24                                         ______________________________________                                    

The higher D-max and accompanying lower speed of make variation numbertwo which is obtained with the same amount of chemical fogging agent asthe control make number one is indicative of greater sensitization,i.e., easier change obtained in make number two containing III.

EXAMPLE C

A commercial lithofilm was exposed for four seconds through a √2 stepwedge and a 100 line square dot gray screen to produce test films. Testfilms were developed for 2 minutes at 80°F in a commercial lithodeveloper as a control, and in the same developer to which 100 mg/literof1,2,3,4,6,7,8,9-octahydro-5H-4a-azonia-2a,7,9a-triazacycloocta[cd]pentalenechloride hydrochloride had been added. The base fog of the control hadan optical density of 0.08 compared with 0.04 when the additive wasused. Table I shows the results obtained for the differing steps.

                  TABLE I                                                         ______________________________________                                                   Optical Density                                                    Step No.     Control       With Additive                                      ______________________________________                                        2            0.03          0.00                                               3            0.50          0.05                                               4            1.24          0.94                                               5            2.03          1.99                                               6            2.89          2.83                                               7            3.98          3.95                                               8            5.08          5.29                                               9            5.65          5.59                                               10           5.64          5.68                                               ______________________________________                                    

From the data of Table I the speed of the developer with additive was98.5 compared with a value of 100 for the control. Contrast was 6.43compared with 5.34 for the control. The data show that the toe of theoptical density/exposure curve was substantially diminished by thepresence of the additive.

We claim:
 1. A compound having the formula ##SPC6##and salts thereofwith an acid selected from the group consisting of hydrochloric,sulfuric, nitric, acetic, tartaric and lactic.
 2. A compound of claim 1in the form of a salt with one equivalent of said acid.
 3. The compoundof claim 2 wherein said acid is hydrochloric acid.
 4. A compound ofclaim 1 in the form of a salt with two equivalents of said acid.
 5. Thecompound of claim 4 wherein said acid is hydrochloric acid.